# HIV Vaccine Candidate Glycopeptide Immunogens

> **NIH NIH R43** · CHEMITOPE GLYCOPEPTIDE, LLC · 2020 · $299,591

## Abstract

HIV vaccines employing the Envelope glycoprotein (Env) as an immunogen have not met their initial promise, in
part, because this approach has failed to induce a broadly neutralizing antibody (bnAb) response. Our key
innovation is the generation and use of homogeneous glycopeptide immunogens to initiate and focus
an immune response against the HIV envelope glycoprotein. These glycopeptide immunogens will form the
basis of an HIV vaccine.
HIV evades neutralization by displaying many epitopes that result in a dominant non-neutralizing response in
humans. However, over the last ten years, dozens of broadly neutralizing antibodies and their cognate epitopes
have been discovered and rigorously characterized, thus providing a roadmap to develop potential vaccines.
The glycopeptides and candidate immunogens produced by Chemitope leverage these discoveries and faithfully
mimic the essential structural features of these broadly neutralizing epitopes by adopting the targeted structure
and by displaying a defined glycosylation pattern. Therefore, our immunogens 1) focus the immune response by
binding with high affinity to low-frequency unmutated common ancestor (UCA) precursor B cells, 2) guide these
B cells toward mature breadth and potency and 3) avoid building a non-productive immune response to the
distracting, non-neutralizing epitopes. Previously, we have synthesized several candidate immunogens derived
from the first and second variable region of Env, V1V2. Our most recent lead pre-clinical candidate V1V2 GPd
displays excellent antigenicity toward the inferred UCA and mature bnAbs PG9 and CH01. Unfortunately, the
antigenic conformation of this glycopeptide is unstable in vivo. Solving this conformational instability is the focus
of this proposal.
In this project, we will develop candidate immunogen glycopeptides that will be chemically stable and retain
antigenicity throughout vaccine formulation. Folding conditions will be developed to draw each glycopeptide into
the desired stable conformation, locked through covalent bond-formation. Feasibility will be evaluated for our
most promising glycopeptide constructs in CH01 UCA knock-in mice to determine if they are viable vaccine
candidates.
Aim I: Synthesize a series of linear V1V2 Glycopeptide Immunogens.
Aim II: Chemically lock the V1V2 Glycopeptide Immunogens in the antigenic conformation.
Aim III: Initiate the expansion and maturation of CH01 UCA B cells in a transgenic mouse model.

## Key facts

- **NIH application ID:** 9981641
- **Project number:** 5R43AI147741-02
- **Recipient organization:** CHEMITOPE GLYCOPEPTIDE, LLC
- **Principal Investigator:** Baptiste Aussedat
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $299,591
- **Award type:** 5
- **Project period:** 2019-07-22 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981641

## Citation

> US National Institutes of Health, RePORTER application 9981641, HIV Vaccine Candidate Glycopeptide Immunogens (5R43AI147741-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9981641. Licensed CC0.

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